Time measurement device, method for measuring time, and inspection device

Abstract

To provide a flow passage device which can measure a predetermined time.SOLUTION: A time measurement device 10 includes: a flow passage groove 12 in at least one surface of a substrate 11; a coating material covering the flow passage groove 12; and a fluid introduction port 14 communicated with the flow passage groove 12. The flow passage groove 12 has a section with a width of 0.8-2.0 mm and with a depth of 70-100 μm. A predetermined time can be measured by a time required for a fluid introduced in the introduction port 14 to arrive at a predetermined destination G in the downstream of the flow passage groove 12.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a timekeeping device, a timekeeping method, and an inspection device.

Background Art

[0002] There is known a flow path device that provides a flow path on a substrate and performs biochemical measurement or chemical synthesis by flowing a fluid through the flow path. In particular, microanalysis devices and microreaction devices manufactured using microfabrication technology are preferably used from the viewpoints of miniaturization, portability, small sample volume, small reagent volume, small waste liquid volume, rapidity, etc.

[0003] For example, International Publication No. 2012 / 060186 (Patent Document 1) discloses a microchannel chip including a resin substrate having a flow path groove on one surface and a resin film joined to the resin substrate so as to cover the flow path groove. This microchannel chip is manufactured by joining a substrate having a groove for a flow path and a coating material covering the groove, and is used as part of an inspection device capable of performing gene analysis using polymerase chain reaction (PCR) or electrophoresis. In the above-described inspection device, first, target DNA in a sample is amplified (gene amplification) by gene analysis (PCR method) using PCR in the reaction chamber of the microchip. Thereafter, in a detection region communicating with the reaction chamber via a microchannel, the target substance contained in the generated liquid is optically detected.

[0004] On the other hand, in recent years, as a rapid diagnostic method for viruses and bacteria such as the novel coronavirus, an inspection kit using a nucleic acid amplification method has been commercially available. The nucleic acid amplification method is performed according to the following procedure. (1) A nucleic acid amplification reagent that acts to amplify a part of the gene of a virus is prepared, and a sample (such as saliva or nasopharyngeal swab) is added to the nucleic acid amplification reagent. (2) An amplification reaction of the gene (nucleic acid) of the virus in the sample is performed by the nucleic acid amplification reagent. (3) The gene of the virus amplified several tens of thousands of times by the reaction with the nucleic acid amplification reagent is detected. The PCR method described above is also one type of nucleic acid amplification method.

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] International Publication No. 2012 / 060186 [Summary of the Invention] [Problems to be Solved by the Invention]

[0006] In the gene (nucleic acid) amplification reaction in the sample in the step (2), a predetermined reaction time usually set between 10 and 60 minutes is required. If this predetermined reaction time is not observed by the user of the inspection device, there may arise a problem that accurate inspection results cannot be obtained. Further, the inspection device of Patent Document 1 only performs the amplification reaction and detection of the target DNA in the microchannel chip, and the reaction time cannot be measured.

[0007] Therefore, a flow path device capable of measuring a predetermined time is desired. [Means for Solving the Problems]

[0008] To achieve the above object, the characteristic configuration of the timing device according to the present invention includes a flow path groove formed on at least one surface of a substrate, a coating material covering the flow path groove, and a fluid inlet communicating with the flow path groove, wherein the flow path groove has a section with a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, and a predetermined time can be measured based on the required time until the fluid introduced into the inlet reaches a predetermined end point located downstream of the flow path groove.

[0009] In order to achieve the above object, a characteristic configuration of the timekeeping method according to the present invention includes a flow channel groove formed on at least one surface of a substrate, a coating material covering the flow channel groove, and a fluid inlet communicating with the flow channel groove. The timekeeping method uses a timekeeping device having a section where the flow channel groove has a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm. When the fluid is introduced into the inlet, the measurement of a predetermined time is started, and when the fluid reaches a predetermined end point located downstream of the flow channel groove, it is determined that the predetermined time has elapsed.

[0010] As a result of intensive research, the inventors have found that in a flow channel device including a flow channel groove formed on at least one surface of a substrate, a coating material covering the flow channel groove, and a fluid inlet communicating with the flow channel groove, by setting the flow channel groove within a specific range having a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, it is possible to suppress variations in the flow velocity of the fluid introduced into the flow channel. According to these configurations, since there is a section of the width and depth of the flow channel groove within a specific range, variations in the flow velocity can be suppressed. Therefore, when the fluid is introduced into the inlet of the flow channel device, the measurement of a predetermined time is started, and when the fluid reaches a predetermined end point located downstream of the flow channel groove, it can be determined that the predetermined time has elapsed.

[0011] Furthermore, a characteristic configuration of the inspection apparatus according to the present invention includes a timing unit that causes at least the specimen to flow out after a predetermined time when a fluid and a specimen are introduced, and a detection unit that can detect the specimen flowing out from the timing unit. The inspection apparatus is configured such that the timing unit includes a flow path groove formed on at least one surface of a substrate, a covering material covering the flow path groove, a fluid receiving portion communicating with the flow path groove into which the fluid is introduced, a specimen receiving portion communicating with the flow path groove into which the specimen is introduced, and an outlet located downstream of the flow path groove that causes at least the specimen to flow out. The flow path groove has a section with a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm. When the fluid is introduced into the fluid receiving portion and the specimen is introduced into the specimen receiving portion, at least the specimen is configured to flow out from the outlet after the predetermined time. The detection unit is in fluid communication with the outlet, and the predetermined time is regulated by the required time until the fluid introduced into the fluid receiving portion reaches a predetermined end point located downstream of the flow path groove.

[0012] According to this configuration, since the timing unit having a section of the flow path groove with a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm is provided, and the detection unit automatically detects the specimen flowing out from the timing unit, the reaction time of the specimen can be made substantially constant, and the inspection accuracy of the inspection apparatus can be improved.

[0013] Hereinafter, preferred embodiments of the present invention will be described. However, the scope of the present invention is not limited by the preferred embodiment examples described below.

[0014] As one aspect, the timing device according to the present invention is preferably configured such that the required time is within an allowable error of ±5% of the predetermined time.

[0015] According to this configuration, the predetermined time can be measured approximately accurately by the timing device according to the present invention.

[0016] As one aspect, the timing device according to the present invention preferably has a hydrophilic portion of at least one of the flow path groove and the covering material that comes into contact with the fluid passing through the flow path groove.

[0017] According to this configuration, even if not all the portions with which the fluid passing through the flow path groove comes into contact are made hydrophilic, at least one of the flow path groove and the coating material may be made hydrophilic, so that the formation of the flow path may be facilitated. That is, when the substrate on which the flow path groove is formed is a hydrophobic resin, the coating material may be made hydrophilic, and when the surface of the flow path groove is hydrophilic, the coating material may be hydrophobic. Conventionally, a hydrophilization treatment such as plasma treatment has been performed on the surface of the flow path groove of a substrate made of a hydrophobic resin and covered with a hydrophobic coating material. However, if a coating material more hydrophilic than the original coating material is used, the hydrophilization treatment such as plasma treatment does not have to be performed on the surface of the flow path groove, so that the process of forming the flow path can be simplified.

[0018] As one aspect, the timepiece according to the present invention preferably further has another section where the depth is larger than that of the said section in the flow path groove.

[0019] According to this configuration, the flow velocity can be reduced by another section with a large depth, and a long time can be measured without increasing the size of the device. Therefore, a long time (for example, 10 to 30 minutes) can be set as the predetermined time.

[0020] As one aspect, the inspection apparatus according to the present invention includes a liquid sample introduction port which is the fluid receiving portion and the sample receiving portion into which the inspection liquid containing the fluid and the sample is introduced, and the predetermined end point is preferably the outlet.

[0021] According to this configuration, since the inspection liquid is used for the time measuring portion, it is easy to make an inspection apparatus with a simple configuration.

[0022] As one aspect, the inspection apparatus according to the present invention includes a fluid introduction port which is the fluid receiving portion and is located upstream of the outlet, and a sample introduction port which is the sample receiving portion and is located downstream of the fluid introduction port and is in fluid communication with the outlet, and the predetermined end point is preferably the sample introduction port.

[0023] According to this configuration, when the viscosity of the test fluid is particularly high, etc., the fluid inlet and the sample inlet are separated, and another fluid with a low viscosity (for example, water, buffer solution, etc.) can be applied to the timing unit. Although the inspection device of the present invention is less affected by factors such as viscosity and can use the test fluid for the timing unit, the time measurement accuracy can be further improved by introducing the timing fluid into the fluid inlet. The sample can be separately reacted at the sample inlet downstream of the fluid inlet and finally configured so that at least the sample flows out from the outlet.

[0024] In one aspect, it is preferable that at least a part of the cross-section of the sample in the outflow direction of the outlet of the inspection device according to the present invention is hydrophilic.

[0025] According to this configuration, since the sample flowing out from the outlet is quickly introduced into the detection unit from the outlet, the gap between the required time measured by the timing unit after introducing the fluid and the sample and the time until the sample is actually detected by the detection unit can be reduced.

[0026] Further features and advantages of the present invention will become clearer from the following description of exemplary and non-limiting embodiments described with reference to the drawings.

Brief Description of the Drawings

[0027]

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[0028] 1. First Embodiment <<Inspection Device 1>> The inspection device 1 according to the first embodiment of the present invention will be described with reference to FIGS. 1 to 5. The inspection device 1 includes a timekeeping unit 10 and a detection unit 20 capable of detecting the test liquid flowing out from the timekeeping unit 10. The inspection device 1 is used, for example, as an inspection kit for infectious disease inspections caused by viruses, bacteria, etc. When a test liquid containing a reaction reagent and a sample is introduced into the test liquid inlet 14, the sample (target substance) after the reaction is detected by the detection unit 20 after a predetermined time. The inspection device 1 according to the present embodiment is used with the side where the test liquid inlet 14 and the outlet 15 are open (the front side in FIG. 1) on the upper side and the side where the coating material 13 is laminated (the back side in FIG. 1) on the lower side. In the following description, when referring to the direction of the inspection device 1, it refers to the vertical direction based on the posture in which the inspection device 1 is placed (the posture shown in FIGS. 2, 3, and 4) so that the coating material 13 is grounded. Also, when referring to the horizontal direction of the inspection device 1, it refers to the direction orthogonal to the above vertical direction (that is, the left-right direction in FIGS. 2, 3, and 4 or the direction orthogonal to the paper surface). Also, the depth direction is the same as the vertical direction. In this specification, the terms "sample" and "test liquid" are used regardless of before and after the reaction and the degree of progress of the reaction.

[0029] [Timekeeping Unit] The timing unit 10 (an example of a timing device) has a function of measuring a predetermined reaction time for reacting a specimen and a reaction reagent. This is because the time (required time) for the specimen fluid containing the fluid and the specimen to flow through the flow channel groove 12 is regulated to a preset time (predetermined time).

[0030] As shown in FIG. 2, the timing unit 10 includes a flow channel groove 12 formed on one surface of a substrate 11, a coating material 13 covering the flow channel groove 12, and a specimen fluid inlet 14 (an example of an inlet) communicating with the flow channel groove 12. The space formed by the flow channel groove 12 and the coating material 13 serves as a flow channel through which the fluid passes.

[0031] In the present embodiment, the substrate 11 includes a through hole that communicates with the flow channel groove 12 and penetrates the substrate 11 at one end of the flow channel groove 12. As shown in FIG. 2, the through hole located upstream of the flow channel groove 12 is the specimen fluid inlet 14. On the other hand, the other end of the flow channel groove 12 includes a notch that penetrates the substrate 11. The notch located downstream of the flow channel groove 12 serves as the flow outlet 15 of the specimen fluid. The flow outlet 15 is in fluid communication with the detection unit 20.

[0032] The flow channel groove 12 has a first section L1 with a width W1 of 0.8 to 2.0 mm and a depth D1 of 70 to 100 μm. If the width W1 and the depth D1 of the flow channel groove 12 are within this range, variations in the flow velocity of the specimen fluid flowing through the flow channel can be suppressed.

[0033] The sample liquid inlet 14 is a fluid receiving part and a sample receiving part into which a sample liquid containing a fluid and a sample is introduced. When a sample liquid containing the sample and the fluid before the reaction is introduced into the sample liquid inlet 14, the timing unit 10 is configured such that the flow rate is regulated by the first section L1, and after a predetermined time, the sample liquid containing the sample after the reaction flows out from the outlet 15. That is, the length of the flow path groove 12 and the like are set so that a predetermined time can be measured based on the required time until the sample liquid introduced into the sample liquid inlet 14 reaches the outlet 15 (an example of a predetermined end point). In the present embodiment, the outlet portion of the sample liquid inlet 14 serves as the starting point S, and the inlet portion of the outlet 15 serves as the end point G. The sample liquid inlet 14 is not limited in shape and size as long as it can introduce a sample liquid containing a fluid and a sample into the flow path groove 12. In the present embodiment, it is a circular hole with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). The upper part of the sample liquid inlet 14 is open, and the lower part is covered with the same covering material 13 as the covering material 13 that covers the flow path groove 12.

[0034] The width W1 of the flow path groove 12 is preferably 0.8 to 1.5 mm, and more preferably 0.9 to 1.2 mm. Also, the depth D1 of the flow path groove 12 is preferably 90 to 100 μm, and more preferably 95 to 100 μm.

[0035] In the present embodiment, the cross-sectional shape of the flow path groove 12 is a quadrangle (particularly a rectangle), but the shape is not limited. The cross-sectional shape of the flow path groove 12 may be a trapezoid or a semi-circle. In particular, if the side on the opening side (the covering material 13 side) is made larger than the side of the groove bottom of the flow path groove 12 to form a trapezoid, it is easy to manufacture the flow path groove 12 with a mold. In the case of such a shape, the above-mentioned width W1 and depth D1 of the flow path groove 12 refer to the maximum width and maximum depth of the flow path groove 12.

[0036] The flow path groove 12 constituting the flow path has, in the present embodiment, five parallel straight line sections and four arc-shaped curved line sections connecting the five straight line sections. The sample liquid introduced into the sample liquid inlet 14 is configured to make four U-turns on the substrate and reach the outlet 15.

[0037] In this embodiment, the first section L1 starts from the starting point S and extends to a point P in the middle of the fifth straight section. Continuously following the first section L1, there is a second section L2 that is deeper than the flow channel groove 12A of the first section L1. In this embodiment, the depth D2 of the flow channel groove 12B of the second section L2 is set to be 2 to 10 times (for example, 6 times) the depth W1 of the flow channel groove 12A of the first section. The width W2 of the flow channel groove 12B of the second section is the same as the width W1 of the flow channel groove 12A of the first section. By having the second section L2, the flow velocity can be effectively reduced, and a long time can be set as a timer for measuring a predetermined time.

[0038] The point P, which is the switching point from the flow channel groove 12A of the first section L1 to the flow channel groove 12B of the second section L2, has an inclined surface 12C as shown in FIG. 4. In this embodiment, the angle θ of the inclined surface 12C is set to 100°. The flow channel groove 12A of the first section L1 rapidly expands from the depth D1 to the depth D2. This is a so-called rapid expansion pipe. When the test liquid enters the flow channel groove 12B, the flow of the test liquid cannot immediately follow the flow channel shape and entangles the surrounding test liquid, forming a vortex in the rapid expansion part. Since this vortex is a flow that stays in place, pressure loss occurs. In this embodiment, this pressure loss is utilized to reduce the flow velocity of the test liquid. The angle θ of the inclined surface 12C is not particularly limited, but is preferably 95° to 105°.

[0039] The ratio of the lengths of the first section L1 and the second section L2 (the length of L1: the length of L2) is preferably 9:1 to 5:5. With such a ratio, the effect of suppressing the variation in time in the first section L1 is easily obtained for the entire timing unit 10.

[0040] In this embodiment, the time required to pass through the above-described timing unit 10 is configured to be within an allowable error of ±5% of the predetermined time.

[0041] Next, each constituent material of the timing unit 10 will be described.

[0042] The substrate 11 may be made of glass or resin, and its material is not particularly limited. However, in this embodiment, a resin-made substrate is used. As the resin constituting the substrate 11, a resin excellent in heat resistance and transparency can be appropriately selected. The substrate 11 can be made of a resin selected from the group consisting of, for example, polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate. As will be described later, when the flow channel groove 12 is made hydrophilic, after the flow channel groove 12 is formed, a hydrophilic treatment such as plasma treatment may be performed on the flow channel groove 12.

[0043] The outer shape and size of the substrate 11 can be appropriately set in consideration of handleability and the like. For example, if it is a quadrangle (square or rectangle), it is preferably, for example, 10 mm or more and 200 mm or less on one side, and more preferably 10 mm or more and 100 mm or less. The outer shape of the substrate 11 is not particularly limited, and it may be other polygons, a circle, an ellipse, or the like. Also, the thickness of the substrate 11 is not particularly limited, and for example, it can be 5 to 20 mm.

[0044] The resin-made substrate 11 can be produced by a resin molding processing technique using a molding die, and can be produced, for example, by injection molding, transfer molding, or extrusion molding.

[0045] In this embodiment, a resin film is used as the coating material 13. As the resin constituting the coating material 13, it is preferable to appropriately select a resin excellent in heat resistance and transparency.

[0046] In this embodiment, at least one of the flow channel groove 12 and the coating material 13 is hydrophilic at the portion where the fluid passing through the flow channel groove 12 contacts. At the portion where the fluid passing through the flow channel groove 12 contacts, both the flow channel groove 12 and the coating material 13 may be hydrophilic, only the flow channel groove 12 may be hydrophilic, or only the coating material 13 may be hydrophilic. Also, the flow channel groove 12 and the coating material 13 do not necessarily have to be hydrophilic at all portions where the fluid contacts, as long as the fluid can flow through the flow channel due to surface tension.

[0047] When the covering material 13 is made of a hydrophobic resin, for example, the covering material 13 can be made of a resin selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate. Note that the resin constituting the covering material 13 may be the same resin as the resin constituting the substrate 11 or a different resin.

[0048] When the covering material 13 is made of a hydrophilic resin, for example, the covering material 13 can be made of a hydrophilic acrylic resin.

[0049] Note that a hydrophilic portion may be provided by applying a hydrophilic coating to the covering material 13 made of a hydrophobic resin, or a hydrophilization treatment such as plasma treatment may be performed on the covering material 13 made of a hydrophobic resin.

[0050] The thickness of the covering material 13 is not particularly limited, but can be, for example, 0.05 mm or more and 2 mm or less. By being 0.05 mm or more, wrinkles and the like are less likely to occur during bonding, and it is easy to sufficiently seal the flow path groove 12. Also, by being 2 mm or less, it is easy to obtain good followability to the unevenness of the substrate 11.

[0051] The substrate 11 and the covering material 13 are laminated so that the surface of the substrate 11 on which the flow path groove 12 is formed and one surface of the covering material 13 are in contact. The covering material 13 is joined to the substrate 11 so as to cover the flow path groove 12. For the joining of the substrate 11 and the covering material 13, an adhesive layer that becomes a joining layer with the substrate 11 may be provided on the covering material 13 side, or alternatively, the substrate 11 and the covering material 13 may be adhered with an adhesive or the like, or the substrate 11 and the covering material 13 may be pressure-bonded by thermocompression bonding. In this way, a flow path is formed between the substrate 11 and the covering material 13.

[0052] [Detection unit] The detection unit 20 can detect the sample that has flowed out from the timing unit 10, and is directly inserted into the outlet 15 provided on the substrate 11 for use. While the sample liquid passes through the timing unit 10, reactions such as nucleic acid amplification reactions are progressing in the sample in the sample liquid. After reacting for a predetermined time, the sample flows out to the detection unit 20, and the detection unit 20 is configured to automatically detect the sample (target substance) after the reaction. As the detection unit 20, the detection unit of a commercially available inspection kit such as an immunochromatography method can be used. In this embodiment, a detection unit (for example, a nucleic acid chromatographic strip) using chromatographic paper with a conjugate pad is used. If the detection unit 20 uses chromatographic paper with a conjugate pad, it is not necessary to add a developing solution, and since it absorbs the sample liquid, it is easy to suppress the outflow of the sample liquid from the detection unit 20.

[0053] In this embodiment, at least a part of the cross-section in the outflow direction of the sample liquid at the outlet 15 in contact with the detection unit 20 is made hydrophilic. The hydrophilic coating material 13 covering the flow path grooves 12 (12A, 12B) may also extend to the lower surface portion of the outlet 15, or the hydrophilization treatment as described above may be performed on the portion of the substrate 11 at the outlet 15. In the former case, it is also preferable to cover the entire lower surface of the substrate 11 with the hydrophilic coating material 13.

[0054] ≪Inspection method≫ Next, the inspection method using the inspection apparatus 1 will be described. First, a sample liquid is introduced into the timing unit 10. The sample liquid is, for example, a mixture of a sample such as saliva or nasopharyngeal swab collected from a human or an animal and a reaction reagent such as a nucleic acid amplification reagent. After the sample liquid is introduced into the sample liquid inlet 14, when a predetermined time (for example, a preset time such as 20 minutes) has elapsed, it flows out from the outlet and automatically flows into the detection unit 20, and the sample (target substance) is detected in the detection unit 20. As shown in FIG. 5, the inspection result is confirmed by whether both the detection line C and the detection line T appear in the detection unit 20. When both the detection line C and the detection line T appear in the detection unit 20, it is positive, and when only the detection line C appears, it is negative.

[0055] According to the inspection device 1, the test fluid introduced into the timing unit 10 passes through the timing unit 10 over a predetermined time and is automatically introduced into the detection unit 20, so that variations in the test results due to variations in the reaction time can be suppressed. Therefore, it is possible to improve the inspection accuracy while adopting the form of an inspection kit that can be detected simply and in a short time.

[0056] 2. Second Embodiment Next, the inspection device 2 according to the second embodiment of the present invention will be described with reference to FIGS. 6 to 12.

[0057] ≪Inspection Device 2≫ The inspection device 2 is different from the inspection device 1 in that a fluid receiving portion into which a fluid is introduced and a specimen receiving portion into which a specimen is introduced are provided separately at different locations on the substrate. The inspection device 2 is useful when the variation in the viscosity of the test fluid is particularly large, and the fluid for measuring the predetermined time in the timing unit 30 and the test fluid to be reacted in the reaction tank are arranged separately. Note that members having the same functions as those in the previous embodiment and not greatly different in shape are denoted by the same reference numerals.

[0058] As shown in FIG. 6, the timing unit 30 in the inspection device 2 is located upstream of the outlet 35, and includes a fluid inlet 31 which is a fluid receiving portion, and a specimen inlet 32 which is a specimen receiving portion located downstream of the fluid inlet 31 and in fluid communication with the outlet 35. The specimen inlet 32 is provided at the end point G for measuring the predetermined time in the timing unit 30.

[0059] As shown in FIG. 7, in the present embodiment, the specimen inlet 32 is provided at a position on the substrate 11 that communicates directly with the outlet 35, and the flow path groove 12, the specimen inlet 32, and the outlet 35 are configured to intersect at one location. In the inspection device 2, this intersection point (connection portion X) serves as the end point G of the fluid. In the inspection device 2, the outlet 35 indicates the portion downstream from the connection portion X.

[0060] The sample introduction port 32 includes a sample reaction tank 33 for allowing a reaction of a sample (e.g., nucleic acid amplification reaction, etc.) to proceed, and a communication groove 34 that communicates the sample reaction tank 33 with the flow path groove 12B. Similar to the fluid introduction port 31, the sample reaction tank 33 is formed as a through hole in the substrate 11, and a hydrophilic coating material 13 extending from the lower surface of the flow path groove 12 is located on the lower surface thereof. The sample reaction tank 33 is kept at a constant temperature (e.g., a predetermined temperature between 25 and 65°C) so that the reaction can be carried out at a constant temperature. The insulation or heating of the sample reaction tank 33 may be performed by placing the entire inspection device 2 in a thermostat or a constant temperature room, or may be performed by contacting only the lower surface of the sample reaction tank 33 with a heating device such as a heater.

[0061] When the pre-reaction sample liquid 18 containing the reaction reagent and the sample is introduced into the sample reaction tank 33 and the fluid 19 is introduced into the fluid introduction port 31 in the inspection device 2, for example, after a lapse of several minutes or more, as shown in FIG. 12, the post-reaction sample liquid 18 automatically flows out from the outlet 35, and the sample (target substance) in the sample liquid 18 is detected by the detection unit 20. That is, the timing unit 30 according to the present embodiment has a timing function for measuring a predetermined reaction time for reacting the sample introduced into the sample reaction tank 33 with the reaction reagent, and has a fluid control function for automatically flowing out the post-reaction sample when the pre-reaction sample is introduced. Hereinafter, the configuration of the timing unit 30 having the fluid control function will be described.

[0062] [Configuration of Timing Unit with Fluid Control Function] As shown in Fig. 8, the timing unit 30 having a fluid control function includes a first flow path 120 having a flow path groove 12 and a coating material 13 (referred to as the first coating material 13 in this embodiment) covering the flow path groove 12, a second flow path 130 having a communication groove 34 and a second coating material 132 covering the communication groove 34, and an outlet 35 that is in fluid communication with the connection portion X between the first flow path 120 and the second flow path 130. Specifically, the second flow path 130 according to this embodiment includes a communication groove 34 formed to open on the surface of the substrate 11 on the side opposite to the flow path groove 12 (the upper surface in Fig. 9) and a second coating material 132 covering the communication groove 34. The timing unit 30 having a fluid control function discharges the sample liquid 18 introduced into and staying in the second flow path 130 and the sample reaction tank 33 by the action of the fluid 19 introduced into the first flow path 120 and causes it to flow out of the outlet 35. In other words, the timing unit 30 having a fluid control function has the function of a passive valve that opens the second flow path 130 under the action of the fluid 19.

[0063] Also in this embodiment, the flow path grooves 12 (12A, 12B) constituting the first flow path 120 have five parallel straight line sections and four arc-shaped curved line sections connecting the five straight line sections. With this configuration, the fluid 19 introduced into the fluid inlet 31 reaches the connection portion X over a predetermined time of several minutes to several tens of minutes (for example, 5 to 60 minutes, etc.) while making four U-turns on the substrate 11. Thus, the first flow path 120 of this embodiment is a timing flow path capable of measuring a predetermined time, and the flow path grooves 12 (12A, 12B) for constituting the timing flow path have the same configuration as the flow path grooves 12 in the timing unit 10.

[0064] In this embodiment, the substrate 11 is formed of a hydrophobic resin, and the surfaces (side surface 12D and top surface 12E) of the flow channel grooves 12 in the first flow channel 120 are hydrophobic (first property). Note that since the bottom surface of the flow channel groove 12 is arranged on the upper side and downward of the substrate 11 as shown in FIG. 9 in the use state of the inspection apparatus 2 to form the top surface, it is hereinafter referred to as the top surface 12E in the following description. The resin component constituting the substrate 11 is not particularly limited, but in this embodiment, it is selected from one or more hydrophobic resins selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth) acrylate, and polyethylene terephthalate. The resin constituting the substrate 11 preferably has one or both of the properties of heat resistance and transparency.

[0065] The surface of the first coating material 13 covering the flow channel groove 12 is hydrophilic (second property). The first coating material 13 only needs to have a hydrophilic surface on at least the side of the flow channel groove 12. In this embodiment, for example, a hydrophilic resin film such as a hydrophilic acrylic resin is used. The resin constituting the first coating material 13 also preferably has one or both of the properties of heat resistance and transparency. Note that a hydrophilic portion may be provided by applying a hydrophilic coating to a coating material made of a hydrophobic resin, or the surface may be made hydrophilic by performing a hydrophilization treatment such as plasma treatment on a coating material made of a hydrophobic resin. In this embodiment, the first coating material 13 covers the entire back surface (lower surface in FIG. 9) of the substrate 11 including the flow channel groove 12. The thickness of the first coating material 13 and the bonding method between the first coating material 13 and the substrate 11 are the same as those in the above-described embodiment.

[0066] In this embodiment, the communication groove 34 is a straight groove that is shallower and shorter than the flow path groove 12B. Specifically, the length of the communication groove 34 is set such that the length of the first flow path 120 from the outlet of the fluid inlet 31 to the connection portion X (referred to as the flow path length M1, not shown in the figure) is greater than the length of the second flow path 130 from the outlet of the specimen reaction tank 33 to the connection portion X (referred to as the flow path length M2) (Fig. 8). In this embodiment, the flow path length M1 is set to be sufficiently long, for example, 10 times or more the length of the flow path length M2.

[0067] The width and depth of the communication groove 34 are not particularly limited, but in this embodiment, for example, the width is set in the range of 0.8 to 2.0 mm and the depth is set in the range of 0.1 to 0.4 mm.

[0068] Since the communication groove 34 is formed in the same substrate 11 as the flow path groove 12, the surface of the communication groove 34 (side surface 34D and bottom surface 34E) is hydrophobic (the first property). In this embodiment, the second coating material 132 uses the same hydrophilic resin film as the first coating material 13, and the surface 132A of the second coating material 132 is hydrophilic (the second property).

[0069] The specimen liquid 18 used in the inspection apparatus 1 of this embodiment is an aqueous solution containing a reaction reagent and a specimen, and an aqueous solution such as water or a buffer solution is used as the fluid 19 introduced into the fluid inlet 31. Since both the specimen liquid 18 and the fluid 19 are hydrophilic liquids in this way, in the first flow path 120, the fluid 19 is repelled on the surface of the flow path groove 12 and shows the property of wetting and spreading on the surface of the first coating material 13. Similarly, the specimen liquid 18 is repelled on the surface of the flow path groove 12 and the surface of the communication groove 34 in the second flow path 130, and shows the property of wetting and spreading on the surfaces of the first coating material 13 and the second coating material 132.

[0070] Therefore, when the fluid 19 is introduced from the fluid inlet 31 into the first flow path 120, the fluid 19 flows through the inside of the first flow path 120 along the surface of the first coating material 13 which is hydrophilic. Similarly, when the specimen liquid 18 is introduced from the specimen reaction tank 33 into the second flow path 130, the specimen liquid 18 flows through the inside of the second flow path 130 along the surface 132A of the second coating material 132 which is hydrophilic.

[0071] The above-mentioned first coating material 13 and second coating material 132 may have different materials, thicknesses, etc. as long as their surfaces are hydrophilic. Also, the bonding method between the substrate 11 and the second coating material 132 may be different from the bonding method between the substrate 11 and the first coating material 13. In this embodiment, since the area of the second coating material 132 is smaller than the area of the first coating material 13, the first coating material 13 may be thermocompression bonded, and the second coating material 132 may be adhered by an adhesive layer or an adhesive.

[0072] As shown in FIG. 9, the first flow path 120 and the second flow path 130 are in fluid communication with each other at the connection portion X because a part of their respective flow path grooves (flow path groove 12B, communication groove 34) intersect. In this embodiment, it intersects substantially at a right angle with the second flow path 130 on the downstream side of the fifth straight section of the first flow path 120.

[0073] The thickness of the substrate 11 in this embodiment is about 0.7 mm. Since the depth D2 of the flow path groove 12B is about 0.6 mm and the depth D3 of the communication groove 34 is about 0.15 mm, the first flow path 120 and the second flow path 130 overlap by about 0.05 mm in the depth direction. With this configuration, a through hole is formed in the substrate 11 at the connection portion X, and the first coating material 13 and the second coating material 132 are located on both surfaces of the through hole.

[0074] The second coating material 132 is disposed at least at a location covering the communication groove 34 of the second flow path 130 on the surface of the substrate 11 on the side opposite to the first coating material 13. In this embodiment, the second coating material 132 is disposed so as to overlap the connection portion X in a plan view of the substrate 11. The second coating material 132 may extend so as to protrude from the communication groove 34 toward the specimen reaction tank 33.

[0075] The fluid inlet 31 is a through hole formed in the substrate 11. Its shape and size are not limited as long as the fluid 19 can be introduced into the first flow path 120. In this embodiment, it is a circular hole with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). The upper part of the fluid inlet 31 is open, and the lower part is covered with a first coating material 13 extending from the first flow path 120.

[0076] Similar to the fluid inlet 31, the specimen reaction tank 33 is a through hole formed in the substrate 11. Its shape and size are not limited as long as the specimen liquid 18 can be introduced into the second flow path 130. In this embodiment, it is a circular hole with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). The upper part of the specimen reaction tank 33 is also open, and the lower part is covered with the first coating material 13. In this embodiment, a reaction reagent is introduced into the specimen reaction tank 33 together with the specimen, and the specimen reaction tank 33 is used as a reaction tank for promoting the reaction of the specimen (for example, nucleic acid amplification reaction, etc.). Therefore, as described above, the specimen reaction tank 33 is kept warm at a certain temperature (for example, a predetermined temperature between 25 and 65 °C) so that the reaction can be carried out at a constant temperature. The warming or heat preservation of the specimen reaction tank 33 may be performed by placing the entire inspection device 2 in a constant temperature bath or a constant temperature room, or by contacting a heating device such as a heater with the lower surface of the specimen reaction tank 33.

[0077] As described above, the outlet 35 indicates the region on the downstream side from the connection portion X, including the downstream of the end of the first flow path 120 and a notch 35A that is in fluid communication with the end of the first flow path 120. The notch 35A opens to one side of the substrate 11 and penetrates in the thickness direction of the substrate 11, and the detection unit 20 is attached thereto. The side wall of the notch 35A exhibits hydrophobicity similar to that of the substrate 11. The open lower surface of the notch 35A is covered with a hydrophilic first coating material 13 extending from the first flow path 120.

[0078] In this embodiment, the first property is hydrophobicity and the second property is hydrophilicity. The first property is the property that the working fluid does not spread (i.e., the repelling property), and the second property is the property that the working fluid spreads. The degree and physical property values are not particularly limited. In this embodiment, the surface of the substrate 11 having hydrophobicity (the first property) has a contact angle with respect to water of, for example, 60° or more and 100° or less. The lower limit value of the contact angle of the substrate 11 with respect to water is preferably 70° or more, more preferably 80° or more. The upper limit value of the contact angle of the substrate 11 with respect to water is preferably 95° or less, more preferably 90° or less. Also, the contact angle of the surface of the first coating material 13 and the second coating material 132 having hydrophilicity (the second property) with respect to water is, for example, 0° or more and 40° or less. The upper limit value of the contact angle of the first coating material 13 and the second coating material 132 is preferably 20° or less, more preferably 10° or less. The contact angle with respect to water in this embodiment is a value measured at 25°C using a commercially available contact angle meter.

[0079] In this embodiment, the first flow path 120 is configured such that the pipe flow resistance is greater than that of the second flow path 130. The pipe flow resistance of the flow path is determined by various conditions. Generally, when the first flow path 120 is longer than the second flow path 130, when the friction coefficient of the flow path is large, when the flow path is narrow, when the flow velocity is large, etc., the first flow path 120 has a greater pipe flow resistance than the second flow path 130. In this embodiment, as described above, the flow path length M1 from the fluid inlet 31 to the connection portion X is sufficiently larger than the flow path length M2 from the specimen reaction tank 33 to the connection portion X, and the pipe flow resistance of the first flow path 120 is greater than the pipe flow resistance of the second flow path 130.

[0080] In the timing unit 30 having the fluid control function according to this embodiment, after the fluid 19 is introduced into the fluid inlet 31 and the specimen liquid 18 is introduced into the specimen reaction tank 33, at least the required time for the specimen liquid 18 to flow out from the outlet 35 is configured to be, for example, within an allowable error of ±5% of the predetermined time.

[0081] ≪Inspection method using the inspection apparatus 2≫ Next, a test method using the test apparatus 2 will be described. In advance, a test fluid 18 and a fluid 19 are prepared. In the test apparatus 2, at the timing of introducing the fluid into the fluid inlet 31, the test fluid 18 is introduced into the specimen reaction tank 33 of the specimen inlet 32. The test fluid 18 is, for example, a specimen such as saliva or nasopharyngeal swab fluid collected from a human or an animal, mixed with a reaction reagent such as a nucleic acid amplification reagent. The introduction of the fluid 19 into the fluid inlet 31 and the introduction of the test fluid 18 into the specimen reaction tank 33 are preferably simultaneous, but may be slightly before or after, and the order of introduction is not particularly limited.

[0082] Into the fluid inlet 31, as the fluid 19, a liquid with a small variation in viscosity, such as water or a buffer solution, and stable physical properties is introduced. The fluid 19 introduced into the fluid inlet 31 passes through the first flow path 120, and a measurement for a predetermined time is performed. In this embodiment, since the timing fluid 19 is used in this way, it is easier to further improve the time measurement accuracy in the timing unit 30. It is preferable that the required time for the fluid 19 introduced into the fluid inlet 31 to reach the connection portion X is within the allowable error of ±5% of the predetermined time. The fluid 19 also functions as a fluid control fluid for flowing out the test fluid 18 remaining in the second flow path 130 and the specimen reaction tank 33 to the outlet 35. Both the test fluid 18 and the fluid 19 are hydrophilic.

[0083] While the measurement for a predetermined time is being performed by the fluid 19, in the specimen reaction tank 33, the reaction (such as a nucleic acid amplification reaction) of the specimen in the test fluid 18 proceeds. If necessary, the entire test apparatus 2 or the specimen reaction tank 33 is heated to, for example, 25 to 65°C. A part of the test fluid 18 in which the reaction has proceeded in the specimen reaction tank 33 fills the second flow path 130 and is in a state of bulging out by surface tension from the second flow path 130 toward the connection portion X.

[0084] In that state, when the measurement fluid 19 arrives at the connection portion X, the test fluid 18 that has come into contact with the fluid 19 flows out from the outlet 35 with priority over the fluid 19 that has passed through the timing unit 30. In this way, also in the test apparatus 2, after a predetermined time, the test fluid 18 containing the specimen flows out from the outlet 35, and the specimen that has flowed out from the outlet 35 is detected by the detection unit 20.

[0085] Next, in association with the functions and operations of the timing unit 30 having a fluid control function in the inspection apparatus 2, the inspection method using the inspection apparatus 2 will be described in more detail.

[0086] First, the fluid 19 is introduced into the fluid inlet 31, and the specimen liquid 18 is introduced into the specimen reaction tank 33. Then, as shown in FIGS. 10 and 11, a part of the specimen liquid 18 flows out of the specimen reaction tank 33 with the surface 132A of the second coating material 132 in the second flow path 130 serving as a guide, fills the second flow path 130, and is guided to the connection portion X. Then, the specimen liquid 18 forms droplets 18A at the connection portion X. In this embodiment, the droplets 18A spread wet on the surface 132A of the second coating material 132 above the connection portion X and are held on the surface 132A of the second coating material 132 in a state of hanging downward due to surface tension and gravity. At this time, the droplets 18A do not contact the first coating material 13. Even if the droplets 18A contact the side surface 12D and the top surface 12E of the flow path groove 12 and the side surface 34D and the bottom surface 34E of the communication groove 34, these surfaces are all hydrophobic, so the droplets 18A do not spread wet and become round droplets due to surface tension. With this configuration, it is possible to suppress the specimen liquid 18 from flowing out of the outlet 40 before the droplets 18A come into contact with the fluid 19.

[0087] On the other hand, when the fluid 19 is introduced into the fluid inlet 31, it starts from the starting point S and flows through the first flow paths 120 (120A, 120B) until it reaches the connection portion X over a predetermined time (for example, a preset time such as 20 minutes). The first flow path 120 according to this embodiment has a timing function as described above and can regulate a predetermined time based on the time required to pass through the first flow path 120, and the reaction between the specimen and the reaction reagent in the specimen liquid 18 proceeds during the predetermined time.

[0088] Next, the fluid 19 that has passed through the first flow path 120 over a predetermined time reaches the connection portion X and contacts the droplet 18A. Then, as shown in FIG. 12, at least the specimen liquid 18 flows out from the outlet 35. In this way, the fluid 19 that has passed through the first flow path 120 acts to cause the specimen liquid 18 remaining in the second flow path 130 and the specimen reaction tank 33 to flow out to the outlet 35. The fluid 19 that has passed through the long first flow path 120 (120A, 120B) of the flow path loses pressure (propulsive force) due to friction with the wall surface in the flow path until it reaches the connection portion X. Therefore, at the connection portion X, the outflow of the specimen liquid 18 from the second flow path 130 is prioritized over the outflow of the fluid 19 in the first flow path 120. The timing unit 30 having a fluid control function is also called a "surface tension valve" that utilizes surface tension because, at the connection portion X where the two flow paths are connected, the fluid that has passed through one flow path breaks the balance of the surface tension of the fluid in the other flow path and opens the other flow path.

[0089] According to the timing unit 30 having a fluid control function according to the present embodiment, without performing an operation for opening the second flow path 130 from the outside, the specimen liquid 18 in the second flow path 130 can be discharged to the outlet 35 by the action of the fluid 19 introduced into the first flow path 120 formed in the same substrate 11. Further, in the timing unit 30 having a fluid control function according to the present embodiment, since the second coating material 132 at least partially overlaps the connection portion X in a plan view of the substrate 11, the surface 132A of the second coating material 132 can guide the specimen liquid 18 to the connection portion X. That is, in the timing unit 30 having a fluid control function, the surface 132A of the second coating material 132 in the second flow path 130 serves as a guide portion for guiding the specimen liquid 18 to the connection portion X.

[0090] The timing unit 30 having a fluid control function according to this embodiment is configured such that the channel length M1 of the first channel 120 from the fluid inlet 31 to the connection portion X is greater than the channel length M2 of the second channel 130 from the sample reaction tank 33 to the connection portion X, and the first channel 120 has a greater pipe resistance than the second channel 130. Therefore, when the fluid 19 that has passed through the first channel 120 contacts the droplet 18A of the sample liquid 18 formed at the connection portion X, the reacted sample liquid 18 flows out from the outlet 35 by itself and flows into the detection unit 20. Since the lower opening of the notch 35A of the outlet 35 is covered with the first coating material 13 having a hydrophilic surface that extends from the first channel 120, the hydrophilic sample liquid 18 can be quickly introduced onto the chromatographic paper with the conjugate pad of the detection unit 20. Through the steps as described above, the sample (target substance) can be detected in the detection unit 20.

[0091] When the fluid 19 reaches the connection portion X, the timing unit 30 having a fluid control function according to the inspection device 2 causes the sample liquid 18 to flow out from the outlet by itself. In this way, the timing unit 30 having a fluid control function opens the second channel 130 under the action of the fluid 19 and discharges the sample liquid 18 without performing control to open the second channel 130 from the outside.

[0092] Furthermore, in the timing unit 30 having a fluid control function according to this embodiment, since the fluid 19 introduced into the fluid inlet 31 passes through the first channel 120 over a predetermined time, the first channel 120 functions as a timer for measuring the reaction time of the sample liquid 18. Therefore, when the sample liquid before the reaction is introduced, the sample liquid 18 that has reacted for a predetermined time can be introduced into the detection unit 50. As a result, variations in the test results due to variations in the reaction time can also be suppressed, and the test accuracy can be improved while being in the form of a test kit that can be detected simply and in a short time.

[0093] [Other Embodiments] In the above embodiment, an example in which the timing device and the timing method are applied as the timing units 10 of the inspection devices 1 and 2 has been described. However, the present invention is not limited to such a configuration, and it may be used for applications that measure a predetermined time as a timer device.

[0094] In the above-described embodiment, an example in which the flow channel groove 12 includes the first section L1 and the second section L2 in this order from the starting point has been described. However, the present invention is not limited to such a configuration, and the second section L2 may be provided before the first section L1, or the second section L2 may be sandwiched between the first sections L1, or the first section L1 may be sandwiched between the second sections L2, etc.

[0095] In the above-described embodiment, an example in which the first section L1 is longer than the second section L2 has been described. However, the present invention is not limited to such a configuration, and the second section may be longer than the first section L1.

[0096] In the above-described embodiment, an example in which the second section L2 has the same width as the first section L1 has been described. However, the present invention is not limited to such a configuration, and the width of the second section L2 may be larger than the width of the first section. For example, the width of the second section L2 may be 2 to 4 times the width of the first section L1.

[0097] In the above-described embodiment, an example in which the inspection device 1 is used as an inspection kit for an infection inspection caused by, for example, a virus, bacteria, etc. has been described. However, the present invention is not limited to such a configuration, and it may be used for other inspections other than those described above.

[0098] In the above-described embodiment, as an example, a configuration has been described in which the inspection device 1 is used with the side where the test liquid inlet 14 and the outlet 15 are open (the front side in FIG. 1) on the upper side and the side where the coating material 13 is laminated (the back side in FIG. 1) on the lower side. However, the arrangement of the timing device and the inspection device according to the present invention is not limited to such an arrangement. For example, the substrate 11 may be inclined at a predetermined angle from the horizontal direction, or the substrate 11 may be erected in the vertical direction. For example, the longitudinal direction of the substrate 11 may be arranged in the vertical direction such that the test liquid inlet 14 is in the upper position and the outlet 15 is in the lower position.

[0099] Similarly, for the inspection apparatus 2 according to the above-described other embodiments, the side where the fluid inlet 31, the specimen inlet 32 (specimen reaction tank 33), and the outlet 15 are open (the front side in FIG. 6) is placed on the upper side, and the side where the coating material 13 is laminated (the back side in FIG. 1) is placed on the lower side, and the configuration used was described as an example. However, the arrangement of the timing device and the inspection device according to the present invention is not limited to such an arrangement. For example, the substrate 11 may be inclined at a predetermined angle from the horizontal direction, or the substrate 11 may be erected in the vertical direction for use. For example, the longitudinal direction of the substrate 11 may be arranged in the vertical direction such that the fluid inlet 31 is in the upper position and the outlet 15 is in the lower position. At this time, a pocket-shaped member with an upper opening may be attached to the opening side of the specimen reaction tank 33 to increase the volume of the specimen liquid 18. Alternatively, a fluid other than the specimen liquid 18 may be stored in the specimen reaction tank 33.

[0100] Hereinafter, a test example will be shown and the timing unit 10 (timing device) in the inspection apparatus 1 of the present embodiment will be described in more detail. However, the scope of the present invention is not limited by the following test examples.

[0101] [Test Example 1] (Creation of Timing Device) A resin substrate made of cycloolefin polymer (COP) ("ZEONOR (registered trademark) 1060R" manufactured by Nippon Zeon Co., Ltd.) with dimensions of 30 mm × 70 mm × 1 mm thickness was cut to form a flow path groove 12 with the shape shown in FIG. 13, and through holes with a diameter of 3 mm serving as a fluid inlet 14 (starting point S) and an outlet 15 (ending point G) located at both ends of the flow path groove 12 were produced. The length L3 of all the flow path grooves 12 was 50 mm, and five flow path grooves 12 having the same width and the same depth were produced on one substrate 11. Thereafter, the surface of the substrate 11 on which the flow path groove 12 was formed was subjected to plasma treatment (hydrophilic treatment) for 10 minutes. Next, the adhesive layer side of a PSA film (using an acrylic adhesive, 125 μm base layer, 7.5 μm adhesive layer) having the same size as the substrate was bonded to the substrate so as to cover the flow path groove, and the substrate and the PSA film were joined to produce a timing device.

[0102] As shown in Table 1, samples 1-1 to 1-8 with the width and depth of the flow path groove changed were produced respectively.

[0103] (Timing method) For each of the five flow channels, 15 μl of +40% sucrose buffer (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v% PEG-20000, 2 mM dithiothreitol, 40 w / v% sucrose) was pipetted into the inlet 14 as the starting point S, and at the same time, the measurement was started with a stopwatch. When it was visually confirmed that the fluid reached the end point G, the stopwatch was stopped, and the time until the fluid reached the end point G was measured.

[0104] The measured time (seconds) is shown in Table 1 together with the sizes of the flow channels of Samples 1-1 to 1-8. The standard deviation was calculated for the five measured times.

[0105] [Table 1]

[0106] As shown in Table 1, for Samples 1-3, 1-4, 1-7, and 1-8 where the flow channels have a width of 0.8 - 2.0 mm and a depth of 70 - 100 μm, the standard deviation of the time taken to flow through the first to fifth flow channels is smaller compared to other samples, and the variation in the required time is small.

[0107] [Test Example 2] When the depth of the flow channel was 100 μm, Samples 2-1 to 2-4 with the width of the flow channel varied as shown in Table 2 were prepared. Similar to Test Example 1, for each of the five flow channels, 15 μl of +40% sucrose buffer (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v% PEG-20000, 2 mM dithiothreitol, 40 w / v% sucrose) was pipetted into the inlet 14 as the starting point S, and at the same time, the measurement was started with a stopwatch. The time (seconds) until the fluid reached the end point G was measured. The results are shown in Table 2.

[0108] [Table 2]

[0109] As shown in Table 2, for Samples 2-3 and 2-4 where the flow channel grooves are within the range of a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, compared with Samples 2-1 and 2-2 outside this range, the standard deviation of the time taken to flow through the first to fifth flow channel grooves was smaller, and the variation in the flow velocity was small.

[0110] [Test Example 3] A timing device was fabricated in the same manner as in Test Example 1, except that the flow channel grooves of the resin substrate were not subjected to plasma treatment and a hydrophilic film (using a hydrophilic acrylic adhesive) was used instead of the PSA film. That is, in Test Example 3, the flow channel grooves are hydrophobic, which is different from Test Example 1 in that the coating material is hydrophilic.

[0111] Samples 3-1 to 3-4 were fabricated with the width of the flow channel grooves being 1.0 mm and the depth being changed as shown in Table 3. For each of the five flow channel grooves in the same manner as in Test Example 1, +40% sucrose buffer (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v% PEG-20000, 2 mM dithiothreitol, 40 w / v% sucrose) (viscosity at 25°C measured with a TV-100E viscometer: 9.382 mPa·s) as the fluid was pipetted into the inlet serving as the starting point S at 15 μl, and at the same time, measurement was started with a stopwatch, and the time until the fluid reached the end point G was measured. The measured time (seconds) is shown in Table 3. Also, the standard deviation was calculated for the five measured times.

[0112]

Table 3

[0113] As shown in Table 3, Samples 3-3 and 3-4, in which the flow channel grooves have a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, had a smaller standard deviation of the time taken to flow through the first to fifth flow channel grooves and a smaller variation in the required time compared to Samples 3-1 and 3-2. Therefore, it was shown that even when the hydrophilic portions contacted by the fluid passing through the flow channel grooves were different, the variation in the flow velocity was small when the flow channel grooves had a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm.

[0114] [Test Example 4] In the timing device of Test Example 3, the fluid introduced into the inlet serving as the starting point S was -sucrose buffer (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v% PEG-20000, 2 mM dithiothreitol) (viscosity at 25°C measured with a TV-100E viscometer: 4.510 mPa·s) for Samples 4-1 to 4-4, and +40% sucrose buffer (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v% PEG-20000, 2 mM dithiothreitol, 40 w / v% sucrose) (viscosity at 25°C measured with a TV-100E viscometer: 9.382 mPa·s) for Samples 4-5 to 4-8, and the time until the fluid reached the end point G was measured. For Samples 4-1 to 4-8, the measured times (seconds) are shown in Table 4. Also, the standard deviation was calculated for the five measured times.

[0115]

Table 4

[0116] As shown in Table 4, even when the viscosity of the fluid changed, Samples 4-3, 4-4, 4-7, and 4-8, in which the flow channel grooves had a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, had a small variation in the flow velocity.

[0117] [Test Example 5] In the timing device of Test Example 3, as shown in Fig. 14, in a flow channel groove with a length of 50 mm, a section L4 with a length of 40 mm from the starting point S was set as a section (the first section) where the width of the flow channel groove was 1.0 mm and the depth was 100 μm, and the depth of the section L5 (the second section) up to the end point G of the remaining 10 mm was changed as shown in Table 5. The section between section L4 and section L5 was set as an inclined surface with an angle θ of 100° shown in Fig. 4. In Test Example 5, three flow channel grooves were fabricated for each sample. For each of them, 15 μl of water purified with Milli-Q (registered trademark) as a fluid was introduced into the inlet 14 serving as the starting point S with a pipetteman, and at the same time, the measurement was started with a stopwatch, and the time until the fluid reached the end point G was measured. The measured time (seconds) is shown in Table 5. Also, the standard deviation was calculated for the three measured times.

[0118]

Table 5

[0119] As shown in Table 5, for samples 5-2 to 5-6 provided with the second section having a greater depth than the first section, the variation in the measurement time was small for all of them, and the flow rate could also be slowed down. In particular, samples 5-4 to 5-6 having a second section with a depth more than four times that of the first section could measure a time more than twice as long as that of sample 5-1 provided with only the first section substantially. In particular, sample 5-6 having a second section with a depth six times that of the first section measured a time about four times as long.

[0120] As described above, the embodiments of the timing device, the timing method, and the inspection device have been described in detail with test examples as specific examples, but the scope of the present invention is not limited to the specific embodiments described above. The embodiments disclosed in this specification are illustrative in all respects, and can be appropriately modified within the scope not departing from the gist of the present invention.

Industrial Applicability

[0121] In addition to being used as a timer for measuring a predetermined time, the timekeeping device of the present invention can be used, for example, as a timekeeping unit of inspection devices for various inspection kits.

Explanation of Reference Numerals

[0122] 1 Inspection device 2 Inspection device 10, 30 Timekeeping unit (timekeeping device) 11 Substrate 12 Flow channel groove 13 Coating material 14 Specimen liquid inlet 15, 35 Outlet 20 Detection unit 31 Fluid inlet 32 Specimen inlet S Starting point G End point W Width of the flow channel groove D Depth of the flow channel groove L1 First section L2 Second section

Claims

1. A flow channel formed on at least one surface of the substrate; A covering material that covers the flow channel; a fluid inlet port communicating with the flow channel; The flow channel has a section having a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, A timing device capable of measuring a predetermined time based on the time required for the fluid introduced into the inlet to reach a predetermined end point located downstream of the flow channel.

2. 2. The timing device of claim 1, wherein the required time is configured to be within a tolerance of ±5% of the predetermined time.

3. 2. The timepiece according to claim 1, wherein a portion of at least one of the flow channel and the covering material that comes into contact with the fluid passing through the flow channel is hydrophilic.

4. 4. The timing device according to claim 1, wherein the flow channel further has another section that is deeper than the section.

5. A flow channel formed on at least one surface of the substrate; A covering material that covers the flow channel; a fluid inlet port communicating with the flow channel; A timing method using a timing device, the flow channel having a section with a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, A timing method in which measurement of a predetermined time begins when the fluid is introduced into the inlet, and the elapse of the predetermined time is determined when the fluid reaches a predetermined destination located downstream of the flow channel.

6. A testing device comprising: a timing unit that, when a fluid and a specimen are introduced, causes at least the specimen to flow out after a predetermined time; and a detection unit that can detect the specimen that has flowed out from the timing unit, The timing unit, A flow channel formed on at least one surface of the substrate; A covering material that covers the flow channel; a fluid receiving portion communicating with the flow channel and into which the fluid is introduced; a sample receiving section communicating with the flow channel and into which the sample is introduced; an outlet located downstream of the flow channel and through which at least the sample flows out; The flow channel has a section having a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, When the fluid is introduced into the fluid receiving portion and the sample is introduced into the sample receiving portion, at least the sample flows out of the outlet after the predetermined time, the detector is in fluid communication with the outlet; An inspection device in which the predetermined time is regulated by the time required for the fluid introduced into the fluid receiving portion to reach a predetermined end point located downstream of the flow channel.

7. The timing unit, a specimen liquid inlet serving as the fluid receiving section and the specimen receiving section, into which the fluid and the specimen liquid containing the specimen are introduced; The inspection apparatus of claim 6 , wherein the predetermined endpoint is the outlet.

8. The timing unit, a fluid inlet located upstream of the outlet and serving as the fluid receiving portion; a sample inlet, the sample receiving portion being located downstream of the fluid inlet and in fluid communication with the outlet; The testing device according to claim 6 , wherein the predetermined destination point is the sample inlet.

9. The testing device according to any one of claims 6 to 8, wherein at least a part of a cross section of the outlet in an outflow direction of the sample is hydrophilic.

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